Currently pathologists rely on labor-intensive microscopic examination of tumor cells using staining techniques originally devised in the 1880's that depend heavily on specimen preparation and that can give false readings. An alternative method is highly desirable. A cellular component that can be potentially useful in diagnosing cellular condition is the mitochondrion. Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. They have been shown to be the primary light-scattering centers for wide-angle scattering and they determine the light-penetration properties of tissues (J. R. Mourant et al., “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Optics Vol 37 (1998) pp. 3586-93). Differences in mitochondria in normal and cancer cells of the same tissue type are manifest in the scattering behavior of the mitochondria.
Mitochondria are most commonly observed in fixed tissue samples as oval particles of 1 to 2 micrometer in length and 0.5 to 1 micrometer in width. The organelle has an outer membrane that encloses the entire contents of the mitochondrion. An inner membrane forms a series of folds called cristae which project inward toward the interior of the organelle. In living cells, as observed by staining mitochondria with rhodamine 123 and performing fluorescence microscopy, mitochondria are dynamic networks of long filamentous structures capable of changing size, form, and location.
Cancer cells have an altered metabolism compared to normal (noncancerous) cells, and mitochondria are involved in many aspects of the altered metabolism of cancer cells. Defects in mitochondrial function have long been suspected to contribute to the development and progression of cancer. A key event in carcinogenesis may involve the development of an “injury” to the respiratory machinery, resulting in compensatory increases in glycolytic ATP production to replace the normal, high-efficiency oxidative phosphorylation as the preferred means of ATP formation. The differences in energy metabolism between normal and cancer cells constitute a biochemical and biophysical basis to speculate that strategies might be developed to selectively identify and kill cancer cells due to their inherently compromised respiratory state. A number of cancer-related mitochondrial defects have been identified and described in the literature.
Mitochondrial hyperplasia can be encountered in tumors from different organs, so-called oncocytomas, and it has been suggested to be related to defective mitochondrial function. Malignant tumor cells with high proliferation index contain fewer mitochondria and, in spite of their higher metabolic activity, they obtain most of their ATP from anaerobic glycolysis, possibly reflecting an adaptive phenomenon to low oxygen concentrations. Conversely, increased numbers of mitochondria resulting in an oncocytic phenotype are usually encountered in benign or low-grade malignant tumors. Oncocytic tumors have been reported in many sites, mainly in kidney, salivary gland, hypophysis, thyroid and parathyroid glands, lung, adrenal gland, and liver. In most of these tumors, mitochondrial hyperplasia is the result of a compensatory mechanism related to abnormalities in mitochondrial function rather than an increase in energy production by tumor cells.